title: Structural plasticity of GABAergic axons is regulated by network activity and GABAA receptor activation.
abstract: Coordinated changes at excitatory and inhibitory synapses are essential for normal brain development and function. It is well established that excitatory neurons undergo structural changes, but our knowledge about inhibitory structural plasticity is rather scarce. Here we present a quantitative analysis of the dynamics of GABAergic boutons in the dendritic region of the hippocampal CA1 area using time-lapse two-photon imaging in organotypic hippocampal cultures from GAD65-GFP mice. We show that ~20% of inhibitory boutons are not stable. They are appearing, disappearing and reappearing at specific locations along the inhibitory axon and reflect immature or incomplete synapses. Furthermore, we observed that persistent boutons show large volume fluctuations over several hours, suggesting that presynaptic content of inhibitory synapses is not constant. Our data show that inhibitory boutons are highly dynamic structures and suggest that inhibitory axons are continuously probing potential locations for inhibitory synapse formation by redistributing presynaptic material along the axon. In addition, we found that neuronal activity affects the exploratory dynamics of inhibitory axons. Blocking network activity rapidly reduces the number of transient boutons, whereas enhancing activity reduces the number of persistent inhibitory boutons, possibly reflecting enhanced competition between boutons along the axon. The latter effect requires signaling through GABAA receptors. We propose that activity-dependent regulation of bouton dynamics contributes to inhibitory synaptic plasticity.
authors.affiliation: Department Synapses, Plasticity, Circuits, Max Planck Institute of Neurobiology Martinsried, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Schuemann
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Klawiter
authors.forename: Tobias
authors.initials: T
authors.lastname: Bonhoeffer
authors.forename: Corette J
authors.initials: CJ
authors.lastname: Wierenga
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology*; D059330:GABAergic Neurons / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009415:Nerve Net / Q000166:cytology / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D017729:Presynaptic Terminals / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology*; D013569:Synapses / Q000502:physiology
chemical_list: D011963:Receptors, GABA-A
keywords: activity-dependent plasticity; bouton dynamics; hippocampal organotypic cultures; inhibitory axons; two-photon microscopy